PEGylated
graphene oxide (GO) has shown potential as NIR converting agent to produce local heat useful in
breast cancer therapy, since its suitable photothermal conversion, high stability in physiological fluids, biocompatibility and huge specific surface. GO is an appealing nanomaterial for potential clinical applications combining drug delivery and
photothermal therapy in a single nano-device capable of specifically targeting
breast cancer cells. However, native GO sheets have large dimensions (0.5-5 μm) such that
tumor accumulation after a systemic administration is usually precluded. Herein, we report a step-by-step synthesis of
folic acid-functionalized PEGylated GO, henceforth named GO-PEG-Fol, with small size and narrow size distribution (∼30 ± 5 nm), and the ability of efficiently converting NIR light into heat. GO-PEG-Fol consists of a nano-GO sheet, obtained by fragmentation of GO by means of non-equilibrium plasma etching, fully functionalized with
folic acid-terminated
PEG2000 chains through amidic coupling and
azide-
alkyne click cycloaddition, which we showed as active targeting agents to selectively recognize
breast cancer cells such as MCF7 and MDA-MB-231. The GO-PEG-Fol incorporated a high amount of
doxorubicin hydrochloride (Doxo) (>33%) and behaves as NIR-light-activated heater capable of triggering sudden Doxo delivery inside
cancer cells and localized
hyperthermia, thus provoking efficient
breast cancer death. The cytotoxic effect was found to be selective for
breast cancer cells, being the IC50 up to 12 times lower than that observed for healthy fibroblasts. This work established plasma etching as a cost-effective strategy to get functionalized nano-GO with a smart combination of properties such as small size, good photothermal efficiency and targeted cytotoxic effect, which make it a promising candidate as photothermal agent for the treatment of
breast cancer.